Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition.

ABSTRACT:

Background

The PI3K pathway is hyperactivated in many cancers, including 70 % of breast cancers. Pan- and isoform-specific inhibitors of the PI3K pathway are currently being evaluated in clinical trials. However, the clinical responses to PI3K inhibitors when used as single agents are not as efficient as expected.

Methods

In order to anticipate potential molecular mechanisms of resistance to the p110α isoform-selective inhibitor BYL719, we developed resistant breast cancer cell lines, assessed the concomitant changes in cellular signaling pathways using unbiased phosphotyrosine proteomics and characterized the mechanism of resistance using pharmacological inhibitors.

Results

We found an increase in IGF1R, IRS1/IRS2 and p85 phosphorylation in the resistant lines. Co-im

SUBMITTER: Leroy C 

PROVIDER: S-EPMC4820873 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature